There are a number of clinical situations in which implants are required. A vascular graft may be desirable in order to replace a section of vessel damage during trauma, or to bypass vessels exhibiting occlusive diseases, for instance, for coronary artery bypass. The two major alternatives available for vascular grafting are the use of an autologous vessel from elsewhere in the body, or the use of biological or synthetic prostheses. Both alternatives have drawbacks. The former may be surgically time consuming and availability limited. Prosthetic materials, while surgically convenient, have a number of performance disadvantages.
Coronary artery bypass grafting remains the most effective longer term treatment for coronary artery disease. Since the introduction of the bypass technique, many different types of vascular grafts have been evaluated. The most obvious source of a vascular conduit is autologous vein or artery removed or transposed from elsewhere in the body. Saphenous vein and internal mammary artery have been used. Saphenous vein conduits suffer from early thrombotic occlusion and also from late failures so that more than 50% have occluded by 10 years. A major drawback with the use of autologous material is that, when occlusion does occur, there is often insufficient autologous conduit left for re-operations. This is particularly relevant when multiple bypass operations are required. Alternatively, saphenous vein may be unavailable, for instance, due to varicosities.
Artificial prostheses constructed from such diverse materials as woven Dacron.TM., Gore-Tex.TM. and expanded microporous polytetrafluoroethylene all suffer to a greater or lesser extent from thrombus formation. Attention has therefore turned towards biological grafts of non-autologous origin.
Allograft veins and arteries from post mortem donors have been used with variable success. However, reliance on this source is unlikely to fulfil demand. To overcome this availability problem, the use of human umbilical veins and arteries has been considered. Unfortunately, these have exhibited poor mechanical performance and rapid occlusion.
Following the successful use of glutaraldehyde preserved animal valves in valve replacement surgery, many groups turned to xenografts as a possible source of vascular replacements. Xenografts need to be chemically modified in order to decrease immunogenicity and increase resistance to resorption. Glutaraldehyde has been the commonest crosslinking agent used. However, its side effects include cytotoxicity which could inhibit endothelial re-colonisation and increased stiffening leading to kinking and a lack of stretch and elasticity. When a less severe crosslinking regimen was used, using aldehyde vapour, only a temporary resistance to degradation was seen. This is likely to lead to an increased risk of aneurysm formation.
U.S. Pat. No. 4,546,500 discloses the preparation of a vessel equivalent from a series of layers of gel contracted from aqueous mixtures of collagen fibrils, a nutrient medium and smooth muscle cells or fibroblast cells. In addition, it has been suggested to include a Dacron.TM. mesh between two layers of the multi-layer structure. The addition of a second layer of collagen resulted in a multi-laminated structure in which the mechanical strength was provided by the Dacron.TM. alone. These blood vessel equivalents, constructed from several layers of collagen and Dacron.TM., have been shown to suffer from delamination problems. The use of fibrin as a biological glue to adhere the collagen layers together has since been employed. It is an object of this invention to overcome this problem.
In addition, it is an object of this invention to improve the preconditioning of the tissue equivalents to the pressures--e.g. blood pressure--to which it will be subjected within the body.